The purpose of this research is to study the biological consequences of disruption of the central nervous system by lesions or pharmacological methods in the neonatal animal. The ontogenic development of central neuronal systems will be modified or prevented by surgical or pharmacological methods at different times following birth. The animals as they mature, will then be studied for the neurochemical, neurophysiological, neuroanatomic, and behavioral consequences of this early disruption of neuronal development. These consequences will be compared to those resulting from the same surgically or pharmacologically-induced lesion placed in the adult animal. The results of such comparisons should allow one to determine (1) if a critical time period exists during which a particular neurochemical system has a significant effect on the ontogeny of the remaining functional systems in brain, (2) the nature of adaptive responses to injury in the neonatal and adult brain, and (3) a better understanding of the fundamental relationships between neuroanatomic and neurochemical ontogenesis and function, which may eventually enable treatment of central nervous system disease with genetic or environmental etiology. Clinical models including hyperserotonemia, associated with mental retardation are included in this Program Project.